The present invention relates to novel 1,4-dihydropyridine derivatives having hypotensive effect.
Heretofore, there have been known, as 1,4-dihydropyridine derivatives, 4-(2-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (U.S. Pat. No. 3,644,627; hereinafter referred to as Nifedipine), 4-(3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid 3-methyl ester 5-.beta.-(N-benzyl-N-methylamino)ethyl ester hydrochloride (Japanese Patent Publication No. 45075/1980; hereinafter referred to as Nicardipine) etc. which are useful as therapeutic agents for improving the coronary circulation or the cerebral circulation.
However, it has been reported based on an animal test that the vasodilating effect and the hypotensive effect resulting from said effect of these compounds disappear within a short period of time, such as 30-40 minutes or so, at the effective intravenous dosage at which they become significant, for example, 10 .mu.g/kg, and also that these compounds have an effect to increase the heart rate which means one element to increase the burden on the function of the heart, in other words, which can also be said a kind of side effect (Arzneimittel-Forschung, Vol. 22, No. 1, p. 33, 1972; ibid., Vol. 26, No. 12, p. 2172, 1976; Toho Igakukai Zasshi, Vol. 26, No. 2, p. 48, 1972). Therefore, when these compounds are to be employed as remedies for hypertension, cardiovascular diseases etc. which require continuous use of drug for a prolonged period of time, the improvement of the preparation, for example, by making it slow-releasing etc., frequent administration, or use in combination with other drugs is needed.